Bioinformatics, Systems Biology and the Omics - Lecture Series

Recent years have seen the rise of systems biology and new sources of large-scale data on biological systems. Obtaining an overview of these activities and future challenges is difficult, since these topics are discussed in a myriad of articles that employ very different approaches. This lecture series aims to give an overview of key elements of this trend. The lecture series has its own home page at If the individual lecturers agree, their slides will be made available at this www-site before the lecture.

This lecture series is inspired by the success of the previous lecture series, The Human Genome and Beyond the Human Genome and is a natural follow-up. The lecture series will be in Michaelmas Term 2005 and take place 2&ndash4PM in Lecture Theatre B in Zoology, South Parks Road.

We hope to see you there.
Jotun Hein.

Date Topic Lecturer Overheads
18/10 The Correlation between Alternative Splicing and Organism Complexity. Gil Ast, Tel Aviv University pdf
25/10 Signalling Networks. Judy Armitage, University of Oxford No slides available yet
1/11 Finding the Molecular Basis of Complex Genetic Variation in Humans and Mice. Richard Mott, University of Oxford part1/part2
8/11 Modelling Spatio-Temporal Pattern Formation in Biology. Philip Maini, Univeristy of Oxford pattern formation/cancer/movie
16/11 Large-Scale Mutagenesis in the Mouse for the Study of Human Disease Steve Brown, University of Oxford Mutagenesis/Phenotyping
22/11 Systems Biology Hans Westerhoff, Universities of Manchester/Amsterdam Systems Biology
29/11 Dissecting Biomolecular Machines: The Single Molecule Approach Achillefs Kapanidis, University of Oxford pdf

October 18th - The Correlation between Alternative Splicing and Organism Complexity - Gil Ast, Tel Aviv University

Alternative splicing of mRNA precursors allows the generation of multiple transcripts and protein products from the same gene. It has been suggested that the impact of this form of gene regulation, which is highest in multicellular organisms, contributes to speciation, and offers a potential explanation for the paradox that the difference in the number of genes between vertebrates and invertebrates is significantly less than expected when compared to the complexity of their proteomes. We suggested the hypothesis that this form of gene regulation is a major evolutionary force leading to the transition to multicellularity, systems complexity and speciation. Studying the evolution of alternative splicing has been difficult until recently. With the advent of comparative and functional genomics, however, it is now possible to exploit a wealth of available sequence information and explore mechanisms of regulation on a large scale in various organisms. Two key questions will be discussed: the contribution of alternative splicing to the evolution of complex genomes - especially human and the evolution of regulatory mechanisms that control alternative splicing decisions.

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October 25th - Signalling Networks - Judy Armitage, University of Oxford

We currently have access to over 200 bacterial genomes and this is expected to increase to over 700 in the next 18 months. Many of the species sequenced cannot be cultured, or can only be grown with difficulty. The challenge for the next decades is to identify the core signalling and metabolic pathways present in bacteria and then the novel pathways that may be of use in, for example, health care, industry or bioremediation. This requires accurate identification of gene products and the development of predictive models of cellular activity under different conditions. The size of the problem is illustrated by the sensory and signalling networks identified to date. Bacteria sense and respond to changes in their environment through spatial and temporal networks of one and two component signalling pathways. Single bacterial cells can have several hundred pathways, some with single targets, others with multiple targets. Identifying which are specific for which physiological change, whether gene expression or differentiation, which can cross talk and when and where each is active, is essential to understanding the response of a specific species to change. The problems and the current approaches and their limitations will be discussed.

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November 1st - Finding the Molecular Basis of Complex Genetic Variation in Humans and Mice - Richard Mott, University of Oxford

In his first talk Richard Mott surveys the state of the art in complex trait analysis, including the use of new experimental and computational technologies and resources becoming available, and the challenges to be faced. He also discusses how the prospects of rodent model systems compare with association mapping in humans. In the second talk, he describes in detail a large-scale project to identify quantitative trait genes in the mouse. This study has measured over 100 phenotypes and genotyped 13000 SNPs on 2000 animals. The analysis of such a complex project involves the integration of statistical genetics, sequence annotation and further functional work.

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November 8th - Modelling Spatio-Temporal Pattern Formation in Biology - Philip Maini, University of Oxford

One of the fundamental problems in developmental biology involves the formation of spatio-temporal patterning. Despite an enormous amount of experimental and theoretical research, a full understanding of how physical and chemical signalling cues are controlled in the correct spatio-temporal sequence still eludes us. In this talk, we will look at some paradigm models that have been proposed to account for tissue-level pattern formation with application to cellular slime mold, pigmentation patterning in fish, and tumour growth.

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November 16th - Large-Scale Mutagenesis in the Mouse for the Study of Human Disease - Steve Brown, University of Oxford

With the completion of the genome sequence of several mammalian organisms, considerable attention is now focused on the functional annotation of these genomes and establishing the relationship between gene and phenotype. The most versatile organism to study mammalian gene function is the mouse as there is an extensive toolkit for modifying the genome and specific genes encompassing gene-driven and phenotype-driven approaches. Underpinning this diversity is the recognition of the utility of a series of mutant alleles at every gene in the mouse genome. Such a resource would enable us to explore fully gene-phenotype space and to provide a wider collection of models for translating mouse gene function to the study of disease genetics in the human. Such programmes will also be critically being dependent upon tools to investigate phenotype. In this talk, I will review progress in these areas as we aim to address one of the critical challenges for 21st century genetics.

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November 22nd - Systems Biology - Hans Westerhoff, Universities of Manchester/Amsterdam

Hans V Westerhoff (1953 - Prof of Systems Biology, AstraZeneca Chair, Manchester Interdisciplinary BioCentre, University of Manchester & Prof of Microbial Physiology, Vrije Universiteit Amsterdam & Prof. Mathematical Biochemistry, University of Amsterdam). He is involved in much of European Systems Biology. Recently Hans Westerhoff moved to Manchester (60% position) to start his second Systems Biology group and a European Systems Biology Laboratory at the Manchester Interdisciplinary Institute. The Amsterdam group already focuses on systems biology using a variety of mathematical biochemistry techniques such as Mosaic Non Equilibrium Thermodynamics, genetic network analysis, kinetic modelling, Metabolic and Hierarchical Control and Regulation Analysis in order to interpret the experimental results.

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November 29th - Dissecting Biomolecular Machines: The Single Molecule Approach - Achillefs Kapanidis, University of Oxford

The living cell is a microcosm comprising sophisticated molecular machines that assemble, disassemble, transport or process biomolecules. To understand how this machinery works, it will be important to move beyond the static views provided by X-ray crystallography, and into real-time, direct observations of individual machines in action. Such detailed observations are becoming a reality through single-molecule detection methods, which can identify and analyze the static and dynamic heterogeneity in biological samples and remove the need for synchronization of the molecules under study. These capabilities allowed single-molecule analysis to unravel complex dynamics and reaction kinetics, and provide unprecedented views of molecular machinery at work, both in vitro and in living cells. I will present examples of the power of the single-molecule approach, with emphasis on studies of machines involved in gene expression, the multi-step path leading from genes on DNA to the synthesis of proteins.

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